Drop In Left Ventricular Ejection Fraction Research Articles

Definition and management of arrhythmia-induced cardiomyopathy: findings from the EHRA SIC survey

Abstract Background Arrhythmia-induced Cardiomyopathy (AiCM) represents a subtype of heart failure (HF) in the context of a sustained arrhythmia. However, clear definitions and management recommendations for AiCM are lacking. Purpose The European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) conducted a survey to determine the current definitions and management of patients with AiCM among European and non-European electrophysiologists. Methods A 25-item online questionnaire was developed and distributed among EP research network centres between September 4th and October 5th 2022. Results Out of the 206 respondents, 16% were females and the most (33%) were between 40-49 years old. Most of the respondents were EP-Specialists (81%) working at a University Hospital (47%). While most participants (67%) agreed that AiCM should be defined as a left ventricular ejection fraction (LVEF) impairment after new onset of an arrhythmia and/or LVEF recovery after treatment of the culprit arrhythmia, only 35% identified a specific LVEF drop/improvement to diagnose AiCM, the majority (50%) agreeing with a 10% change in LVEF (Figure) but with the rest of the experts choosing a wide range of values (from 5 to 20% LVEF drop). Most respondents used all available therapies in AiCM patients: catheter ablation was chosen by 93%, electrical cardioversion by 83%, antiarrhythmic drugs by 76% and adjuvant HF treatment were used by 76%. 83% of respondents indicated that adjuvant HF treatment should be started at first diagnosis of HF prior to antiarrhythmic treatment and 84% agreed that the therapy should be stopped within six months after LVEF normalization. Responses for the optimal time point for the first reassessment of LVEF during FU varied markedly (1 day to over 6 months after antiarrhythmic treatment). Conclusion This EHRA Survey reveals varying practices in defining and managing AiCM among European and non-European physicians. There is an unmet need for a consensus in the definition and management of AiCM patients to improve patient care.Figure

Definition and management of arrhythmia-induced cardiomyopathy: findings from the European Heart Rhythm Association survey.

Arrhythmia-induced cardiomyopathy (AiCM) represents a subtype of acute heart failure (HF) in the context of sustained arrhythmia. Clear definitions and management recommendations for AiCM are lacking. The European Heart Rhythm Association Scientific Initiatives Committee (EHRA SIC) conducted a survey to explore the current definitions and management of patients with AiCM among European and non-European electrophysiologists. A 25-item online questionnaire was developed and distributed among EP specialists on the EHRA SIC website and on social media between 4 September and 5 October 2023. Of the 206 respondents, 16% were female and 61% were between 30 and 49 years old. Most of the respondents were EP specialists (81%) working at university hospitals (47%). While most participants (67%) agreed that AiCM should be defined as a left ventricular ejection fraction (LVEF) impairment after new onset of an arrhythmia, only 35% identified a specific LVEF drop to diagnose AiCM with a wide range of values (5-20% LVEF drop). Most respondents considered all available therapies: catheter ablation (93%), electrical cardioversion (83%), antiarrhythmic drugs (76%), and adjuvant HF treatment (76%). A total of 83% of respondents indicated that adjuvant HF treatment should be started at first HF diagnosis prior to antiarrhythmic treatment, and 84% agreed it should be stopped within six months after LVEF normalization. Responses for the optimal time point for the first LVEF reassessment during follow-up varied markedly (1 day-6 months after antiarrhythmic treatment). This EHRA Survey reveals varying practices regarding AiCM among physicians, highlighting a lack of consensus and heterogenous care of these patients.

Abstract PO5-15-01: Prospective Biomarker Assessment of Cardiotoxicity Among Ethnically Diverse Women with Early Breast Cancer

Abstract Background: Approximately 4.1 million women in the United States are living with breast cancer1. Cardiac dysfunction is a significant adverse effect of commonly used breast cancer therapies like doxorubicin (D) and trastuzumab (T). The cardiotoxicity (CTox) associated with these agents manifests as a reduction in left ventricular ejection fraction (LVEF) with or without signs and symptoms of heart failure. Purpose: The objective of this study is to evaluate serum cardiac and inflammatory biomarkers over time and their association with CTox development. Methods: A total of 133 newly diagnosed stage I-III invasive breast cancer patients were enrolled in a prospective clinical trial (2013-2017) and received standard of care T and/or D based systemic therapy. They underwent serial echocardiograms every 6 months for two years and then based on clinical need for a total of six years. CTox was defined as a >10% drop in LVEF, and/or LVEF < 50%. Biomarker data was collected at baseline, 12 and 24 months and included both cardiac biomarkers (Troponin-I, TN-I and amino terminal B-type natriuretic peptide, NT-proBNP) and measures of inflammation (C-reactive protein, CRP). Of the 32 with CTox patients, 15 had adequate serum samples and were matched with 15 patients without CTox (N=30), controlling for age, race, and treatment regimen prior to serum sample analysis. Results: The mean LVEF at baseline was similar between CTox and non-CTox patients (64% vs 62%, p=0.342). However, over the course of 12 and 24 months, CTox patients experienced a statistically significant decrease in LVEF compared to their baseline values (55% and 56%, respectively, p < 0.001). At baseline, CTox patients had higher CRP levels compared to non-CTox (13.4 mg/L vs 3.35 mg/L), however this difference did not reach statistical significance (P >0.05). Although this difference seemed to narrow at 12 months (3.88 mg/L vs 1.52 mg/L, p< 0.05) and 24 months (6.85 mg/L vs 2.36 mg/L, p< 0.05), CTox patients consistently had higher mean CRP levels. Mean TN-I levels increased at both 12 and 24 months compared to baseline (CTox 1.13 ng/L, 7.13 ng/L, 4.13 ng/L vs non-CTox 0.800 ng/L, 8.13 ng/L, 4.60 ng/L, p< 0.05) but there were no significant differences between the two groups (p >0.05). While baseline NT-proBNP levels did not differ significantly between the CTox and non-CTox patients, there were statistically significant increases in CTox patients at 12 and 24 months (205 pg/mL vs 74 pg/mL, and 200 pg/mL vs 96 pg/mL, p < 0.01, respectively). Conclusion: In a well characterized, diverse, matched subset of patients with early breast cancer who were prospectively followed with serial echocardiograms, distinct biomarker patterns were observed. Measures of inflammation (CRP) at baseline were different and these changes appeared to diminish over time. While the cardiac biomarker TN-I appeared to increase in both +CTox and -CTox group over time, only those with differential NT-proBNP elevations were associated with cardiotoxicity. 1Lisa Gallicchio, PhD and others, Estimation of the Number of Individuals Living With Metastatic Cancer in the United States, JNCI: Journal of the National Cancer Institute, Volume 114, Issue 11, November 2022, Pages 1476–1483 Citation Format: Shahzaad Jahangier, Rubina Qamar, Maharaj Singh, Vinay Thohan, James Weese, Bijoy Khandheria, Anna Kamke-Jordan. Prospective Biomarker Assessment of Cardiotoxicity Among Ethnically Diverse Women with Early Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-01.

Abstract PO4-09-11: Predictors of Cardiotoxicity in Early Breast Cancer Patients Treated with Doxorubicin and/or Trastuzumab: Implications of Race/Ethnicity and Insurance Status

Abstract Predictors of Cardiotoxicity in Early Breast Cancer Patients Treated with Doxorubicin and/or Trastuzumab: Implications of Race/Ethnicity and Insurance Status Shahzaad K Jahangier, MD, Yunqi Liao, MS, Maharaj Singh, PhD, James Weese, MD, Bijoy Khandheria, MD, Anna Kamke-Jordan MS, Vinay Thohan, MD, Rubina Qamar, MD Background: Approximately 4.1 million women in the United States are living with breast cancer1. Cardiac dysfunction is a significant adverse effect of commonly used breast cancer therapies like doxorubicin (D) and trastuzumab (T). The cardiotoxicity (CTox) associated with these agents manifests as a reduction in left ventricular ejection fraction (LVEF) with or without signs and symptoms of heart failure. Purpose: The objective of this study is to identify high-risk populations susceptible to developing CTox, with a focus on identifying individuals who could potentially benefit from the early initiation of empiric cardioprotective therapies. Methods: We investigated the relationship of race/ethnicity, insurance status, treatment regimen and comorbidities including hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), tobacco use, BMI, age, and radiation therapy on the development of CTox from D and/or T. A total of 133 newly diagnosed stage I-III invasive breast cancer patients were enrolled in a prospective clinical trial (2013-2017) and received standard of care D and/or T based systemic therapy. Echocardiogram data was collected every 6 months for two years and then based on clinical need for a total of six years. CTox was defined as a >10% drop in LVEF, and/or LVEF < 50%. Results: Our study included a population of 133 patients comprising Black (22%), White (77%), and Hispanic (1.5%) individuals. Among these patients, 32 developed CTox (Black 41%, White 19%, Hispanic 50%). Of all patients, 29% had State insurance while 71% had Private insurance. Prevalence rates for comorbidities were as follows: HTN (41%), HLD (32%), DM (13%), and tobacco use (36%). In a univariate logistic regression model, race/ethnicity, HTN, insurance status, and tobacco use were most strongly associated with Ctox. When controlling for tobacco use and HTN, race/ethnicity was not significantly associated with Ctox. However, direct comparisons of levels of race/ethnicity showed that Black patients were more likely to develop Ctox when compared to White patients (OR 2.60, 95% CI = 1.01-6.65, P = 0.045). HTN patients were also more likely to develop Ctox, when controlling for ethnicity and tobacco use (OR 2.62, 95% CI = 1.10-6.43, P = 0.031). In a separate multivariate analysis, we examined insurance as a surrogate for socioeconomic status. Having State compared to Private insurance was associated with an increased risk of developing CTox when controlling for race/ethnicity and HTN (OR 3.73, 95% CI = 1.47-9.58, P = 0.006). Furthermore, in all models, HLD, DM, BMI, age, and radiation field were not found to be significantly associated with increased CTox. Conclusion: In our well characterized population of patients with stage I-III breast cancer, who were prospectively followed and received standard of care systemic therapy, we observed an association between insurance status with increased risk of CTox from treatment regimen. 1Lisa Gallicchio, PhD and others, Estimation of the Number of Individuals Living With Metastatic Cancer in the United States, JNCI: Journal of the National Cancer Institute, Volume 114, Issue 11, November 2022, Pages 1476–1483 Citation Format: Shahzaad Jahangier, Rubina Qamar, Vinay Thohan, Maharaj Singh, Yunqi Liao, James Weese, Bijoy Khandheria, Anna Kamke-Jordan. Predictors of Cardiotoxicity in Early Breast Cancer Patients Treated with Doxorubicin and/or Trastuzumab: Implications of Race/Ethnicity and Insurance Status [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-09-11.

Abstract PO2-04-05: FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES

Abstract Background Brain metastases (BM) are a severe complication of HER2-positive metastatic breast cancer. In the absence of any immediate indication for local therapy, the tyrosine-kinase inhibitor tucatinib combined with trastuzumab and capecitabine (TTC) is regarded as the preferred systemic treatment option for active BM, while data on the activity of antibody-drug conjugates (ADC) is limited. In the primary outcome analysis of TUXEDO-1, an intracranial response rate (RR) of 73.3% was reported with the ADC trastuzumab-deruxtecan (T-DXd). Here, we report final progression-free survival (PFS) and overall survival (OS) results of this study. Patients and Methods: TUXEDO-1 is a prospective, single-centre, single-arm phase 2 trial. Adult patients with HER2-positive BC and active BM (newly diagnosed untreated or progressing after prior local therapy), prior treatment with trastuzumab and pertuzumab, ECOG performance status 0 or 1 without indication for immediate local therapy were accrued and received T-DXd until progression, inacceptable toxicity, or withdrawal for any other reason. The primary endpoint was intracranial RR centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria in the intention-to-treat population; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population (PPP). Results A total number of 15 patients were accrued; one patient was found to have dural metastases only upon restaging, resulting in a PPP of 14 patients. Patients had received a median number of two prior treatment lines (range, 1-5), 60% had progressive brain metastases and 60% had received prior T-DM1. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). A total of 238 cycles of T-DXd were administered (median 11.5 cycles; range 4-42). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event (AE) was fatigue (n=3; 20%). A total of 8 serious AEs were reported in 8 patients. Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL and neurocognitive functioning were maintained over the entire treatment duration and a significant deterioration of global QoL was observed upon progression (p=0.036). Most patients received TTC (n=5) or local therapy (n=4) as next subsequent treatment line. Ancillary biomarker studies are ongoing, and results will be presented at the meeting. Discussion In TUXEDO-1, T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive breast cancer BM. The safety profile was consistent with previous reports. T-DXd did not impair QoL and neurocognitive functioning was maintained. Results therefore support the concept of ADCs as systemic therapy for active BM. Citation Format: Rupert Bartsch, Anna Sophie Berghoff, Julia Furtner, Maximilian Marhold, Elisabeth Sophie Bergen, Sophie Roider-Schur, Angelika Maria Starzer, Maximilian Mair, Heidrun Forstner, Beate Rottenmanner, Marie-Bernadette Aretin, Karin Dieckmann, Zsuzsanna Bago-Horvath, Helmuth Haslacher, Georg Widhalm, Aysegül Ilhan-Mutlu, Christoph Minichsdorfer, Thorsten Fuereder, Thomas Szekeres, Leopold Oehler, Birgit Gruenberger, Georg Pfeiler, Christian F. Singer, Ansgar Weltermann, Luzia Berchtold, Matthias Preusser. FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-05.

Abstract 6298: The value of routine trastuzumab-related cardiac toxicity monitoring in gastrointestinal cancers

Abstract Background: It is a common practice to monitor trastuzumab-related cardiac toxicity (TRCT) using left ventricular ejection fraction (LVEF) in patients who receive trastuzumab-containing therapy for human epidermal growth factor receptor 2 (HER2)-positive cancers. However, this monitoring approach does not appear cost effective in patients with HER2-positive gastrointestinal (GI) cancers given poor overall survival (OS). Here, we aim to examine the incidence of clinically significant TRCT in this target population. Methods: This is a retrospective cohort study of patients with advanced HER2-positive GI cancers who received trastuzumab-containing therapies (trastuzumab +/- pertuzumab, chemotherapy +/- immunotherapy + trastuzumab, trastuzumab deruxtecan) between 2011 and 2023. HER2 status was determined by immunohistochemistry, fluorescent in situ hybridization, and/or next generation sequencing. LVEF was estimated by serial transthoracic echocardiograms (TTE). Continuous variables were summarized as median and interquartile range (IQR). Paired Wilcoxon signed rank test was used to compare serial LVEF. OS was estimated using Kaplan-Meier method. Results: A total of 243 patients were included in this study with a median age of 64 (IQR: 55-70) years. 139 (57%) patients had esophageal or GEJ adenocarcinoma; 45 (19%) patients had gastric cancer; 37 (15%) patients had colorectal cancer; and the rest had other GI cancers. Median follow-up time was 18.6 (IQR: 9.2-36) months. Median OS from cancer diagnosis and the first dose of trastuzumab-containing therapy were 24.1 (95%CI: 20.2-30.2) and 11.7 (95%CI: 10.4-15.6) months, respectively. Patients received a median of 13 cycles of trastuzumab-containing therapy for a median duration of 4.1 (IQR: 1.4-10.1) months. The median number of TTE each patient had throughout therapy was 2 (IQR: 1-4). Median baseline LVEF was 61% (IQR: 56-65%) which was significantly higher (p<0.001) than the median lowest LVEF of 58% (IQR: 53-62%) during therapy, but not different (p=0.14) from the most recent median LVEF of 60% (IQR: 56-64%) after discontinuation of trastuzumab. Among 176 patients with serial LVEF data, 16 (9%) had > 10% LVEF drop; 7 (44%) of these 16 patients had LVEF recovery. None of the cardiovascular risk factors prior to trastuzumab treatment including hypertension, diabetes, hyperlipidemia, peripheral arterial disease, coronary artery disease, and stroke were significantly associated with the development of TRCT. Conclusion: The incidence of clinically significant LVEF drop appears low in patients with advanced GI cancers as post-treatment LVEF recovery to baseline was observed at the population level. The value of using TTE to monitor TRCT in these patients with short OS should be further assessed in the perspective of cost effectiveness. Citation Format: Samual R. Kosydar, Matteo Castrichini, Mojun Zhu, Hao Xie. The value of routine trastuzumab-related cardiac toxicity monitoring in gastrointestinal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6298.

Hemodynamic evaluation of extremely low birth weight infants during the first 7 days of life

Background and aimWe aimed to investigate the hemodynamic status of extremely low birth weight (ELBW) infants during the transitional period under intensive management. MethodsThis retrospective cohort study analyzed left ventricular ejection fraction (LVEF), left ventricular end-systolic wall stress (ESWS), left ventricular internal dimension in diastole (LVIDd), and mean arterial pressure (MAP) of ELBW infants during their first week of life. Small for gestational age (SGA), histological chorioamnionitis (hCAM), severe intraventricular hemorrhage (IVH), and non-survival to discharge infants were compared to their counterparts. ResultsSixty-two infants (25.7 ± 2.1 weeks, 700.7 ± 165.4 g) were analyzed. MAP gradually increased. Median LVEF was 69.8 % on day 1, decreased to 62.7 % on day 2, then increased throughout the week. ESWS was lowest at birth, rose to 28.2 g/cm2 on day 2, and decreased on day 6. There were no significant changes in LVIDd. SGA infants had higher MAP throughout, higher LVEF on day 2 and 3, but lower LVEF on day 5 to 7. LVIDd was lower in hCAM group. Severe IVH group had a more significant drop in LVEF on day 2, higher ESWS, and a higher incidence of hemodynamic significant patent ductus arteriosus (hsPDA). Non-survival had lower LVIDd. ConclusionsMAP increased gradually. Hemodynamic instability was observed in the first two days, with decreased LVEF and increased ESWS before stabilization. We observed an alteration in hemodynamic adaptation in SGA and hCAM infants. Severe IVH group experienced early hemodynamic instability and a higher incidence of hsPDA.

Abstract 17444: Racial and Ethnic Disparities in Anthracycline Cardiotoxicity

Introduction: There are limited data on anthracycline cardiotoxicity in racially and ethnically diverse populations. Aims: Our study sought to examine the incidence of cardiotoxicity and the changes in left ventricular ejection fraction (LVEF) in cancer survivors treated with anthracycline in a multiracial/ethnic community. Methods: We included consecutive adult patients who underwent anthracycline-based chemotherapy from 2016 to 2019 for any type of cancer. Patients with preexisting heart failure were excluded. The endpoint was the development of cardiotoxicity (defined as clinical HF or drop in LVEF≥10% to LVEF<53%). Results: Our retrospective cohort included 925 patients (22% Non-Hispanic White (NHW), 25% Non-Hispanic Black (NHB), 31% Hispanic, and 2% Asian). Hypertension, diabetes, and hyperlipidemia were more prevalent in NHB, Hispanic, and Asian patients than in NHW patients. The mean cumulative anthracycline dose was 197±99 mg/m 2 and the mean LVEF was 64±5.7%, both similar across racial and ethnic groups. During a median follow-up of 21 months, 116 patients (13%) developed cardiotoxicity. The incidence of cardiotoxicity was significantly higher in NHB (16%), Hispanic (15%), and Asian (18%) patients compared to NHW patients (7%) (p=0.045). Of the 116 patients with cardiotoxicity, 21 patients had reduced ejection fraction (LVEF<50%) and 81 had preserved ejection fraction (LVEF≥50%). Significantly more Hispanic patients developed cardiotoxicity with reduced ejection fraction (33.3%) compared to NHW (14.3%) and NHB (6.1%) patients (p=0.014). The mean decline in LVEF was higher in NHB patients (4% ± 9%) and Hispanic patients (6% ± 10%) than in NHW patients (3% ± 7%). Conclusions: In a large racially and ethnically diverse cohort of cancer survivors treated with anthracycline-based chemotherapy, NHB and Hispanic patients had an increased risk of cardiotoxicity and a greater decline in LVEF compared to their White counterparts.

Impact of Positron Emission Tomographic Myocardial Perfusion Imaging on Patient Selection for Revascularization

BackgroundPositron emission tomography (PET) myocardial perfusion imaging (MPI) quantifies left ventricular ejection fraction (LVEF) at peak stress. PET LVEF reserve (LVEF-R = stress LVEF − rest LVEF) offers diagnostic and prognostic value. ObjectivesThe purpose of this study was to determine if PET LVEF-R identifies patients with survival benefit postrevascularization. MethodsWe followed 14,649 unique consecutive patients undergoing 82Rb rest/stress PET MPI from January 2010 to January 2016 (excluding known cardiomyopathy). Adjusted Cox models were built to predict all-cause death, and the 3-way interaction of known coronary artery disease (CAD) (prior myocardial infarction/revascularization), LVEF-R, and 90-day revascularization was tested. ResultsKnown CAD was present in 4,982 (34.0%). Ischemia was detected in 5,396 (36.8%; ≥10% in 1,909 [13%]). Mean LVEF-R was 4.2% ± 5.7%, and was ≤0, 1 to 5, and >5 in 3,349 (22.9%), 5,266 (35.9%), and 6,034 (41.2%). Over median follow-up of 3.4 years (IQR: 1.9-5.2 years), 1,324 (8.1%) had 90-day revascularization, and there were 2,192 (15.0%) deaths. In multivariable modeling, there was a significant 3-way interaction among known CAD, LVEF-R, and 90-day revascularization (P = 0.025), such that LVEF-R ≤0 identified patients with survival benefit with 90-day revascularization in those without prior CAD (interaction P = 0.005), independently beyond percent ischemia and myocardial flow reserve. Among patients with known CAD, LVEF-R was not prognostic of death (HR: 0.99; 95% CI: 0.98-1.02; P = 0.98). ConclusionsA lack of augmentation or drop in LVEF with vasodilator stress on PET MPI independently identifies patients who have better survival with revascularization within 90 days post-MPI compared with medical therapy, in absence of prior myocardial infarction or revascularization. Multiparametric assessment of ischemia with PET can optimize post-test management.

Association of leadless pacing with ventricular and valvular function.

Traditional transvenous pacemakers are associated with worsening tricuspid valve function due to lead-related leaflet impingement, as well as ventricular dysfunction related to electromechanical dyssynchrony from chronic right ventricular (RV) pacing. The association of leadless pacing with ventricular and valvular function has not been well established. We aimed to assess the association of leadless pacemaker placement with changes in valvular regurgitation and ventricular function. Echocardiographic features before and after leadless pacemaker implant were analyzed in consecutive patients who received a leadless pacemaker with pre- and postprocedure echocardiography at Duke University Hospital between November 2014 and November 2019. Valvular regurgitation was graded ordinally from 0 (none) to 3 (severe). Among 54 patients, the mean age was mean age was 70.1 ± 14.3 years, 24 (44%) were women, and the most frequent primary pacing indication was complete heart block in 24 (44%). The median RV pacing burden was 45.4 (interquartile range [IQR] 3.5-97.0). On echocardiogram performed 8.9 months (IQR 4.5-14.5) after implant, there was no change in the average severity of tricuspid regurgitation (mean change 0.07 ± 1.15, p = .64) from pre-procedure echocardiogram. We observed a decrease in the average left ventricular ejection fraction (LVEF) (52.3 ± 9.3 to 47.9 ± 12.1, p = .0019) and tricuspid annular plane systolic excursion (TAPSE) (1.8 ± 0.6 to 1.6 ± 0.4, p = .0437). Thirteen patients (24%) had absolute drop in LVEF of ≥10%. We did not observe short term worsening valvular function in patients with leadless pacemakers. However, consistent with the pathophysiologic impact of RV pacing, leadless pacing was associated with a reduction in biventricular function.

Cardiac function of long-responders to dual anti-HER2 antibodies amongst patients with HER2 positive advanced breast cancer.

1043 Background: Dual anti-HER2 antibodies pertuzumab (P) and trastuzumab (T) in combination with taxane (D), followed by PT maintenance, is the standard first line treatment for HER2 positive advanced breast cancer (HER2+ ABC). Treatment associated cardiotoxicity necessitates regular cardiac function surveillance, which is a burden particularly for treatment long-responders. Data for cardiac safety of prolonged P+T exposure is scarce. We investigate the real-world impact on cardiac function in long-responders to treatment with dual anti-HER2 antibodies. Methods: We identified consecutive patients with HER2+ ABC who received the CLEOPATRA regimen (PT-D) between Jan 2014 and Dec 2020 from an institutional cancer registry. All patients had pre-treatment multiple-gated acquisition (MUGA) scan or echocardiogram, and subsequently at 3-monthly intervals until end of treatment to monitor left ventricular ejection fraction (LVEF). Patients on treatment for ≥36 months were considered long-responders. The Wilcoxon signed-rank test was used to assess any significant difference in LVEF at various landmark time-points in comparison to their pretreatment baseline. Results: 101 women with HER2+ ABC were eligible for analysis. Median age at treatment was 62 (IQR, 56.0-69.0). The median duration of treatment was 17.3 months (IQR, 9.0-31.3). 22.8% of patients were long-responders, who received a median of 67 cycles of treatment (IQR, 58-88). Compared to baseline, median LVEF was significantly decreased at 6m (median, 66% vs 69%, p=0.02), however there were no significant differences for any of the subsequent time-points up to 84 m. All of the larger LVEF drop (≥10% from baseline) occurred by the first 24 months, representing 4.7% of the overall measurements. Risk factors present for patients experienced treatment suspension (n=3) included previous exposures to anthracycline and left sided radiotherapy. Conclusions: In patients with HER2+ ABC who were long-responders to first-line PT-D, prolonged exposure to dual anti-HER2 antibodies was not associated with significant cardiotoxicity. It is safe to de-escalate the cardiac surveillance for this population. [Table: see text]

Global longitudinal strain analysis application for prediction of left ventricular dysfunction in breast cancer under sequential therapy

Transthoracic echocardiography (TEE) plays a major role in the baseline assessment and follow-up of cardio-oncology patients. While left ventricular ejection fraction (LVEF) still has its place in cardiac monitoring, new modalities like myocardial deformation imaging with speckle tracking strain analysis has been validated for early detection of subclinical LV dysfunction. We conducted a longitudinal prospective study including all the breast cancer patients treated with anthracyclines and trastuzumab from January 2017 to March 2022. All patients underwent baseline TEE, and were followed-up every 3 months after that, with GLS assessment whenever it was possible. We evaluated the frequency of GLS drop and its correlation to LVEF reduction. Out of a total of 1583 patients, 677 had available LV GLS assessment. Among them, 83 (12.3%) decreased their GLS during follow-up, 67% of which had no concomitant drop in LVEF. In these patients, impaired LV GLS values were noted at 3 months after chemotherapy and at 6, and 12 months compared with baseline (−22.3 ± 1.8% at baseline, −18.1 ± 2.3% at 3 months, −17.7 ± 2.1% at 6 months, and −16.9 ± 2.1% at 12 months). LV GLS at 3 months was strongly correlated to cardiotoxicity (LVEF < 50%) at 12 months (P < 0.05). A cut-off LV GLS value of −16.9% was then retained to identify LVEF alteration at the end of follow-up. Finally, our study found that GLS at 3 months and 6 months had a prognostic value, since the lower GLS was, the poorest the patient's clinical outcome was, with further development of symptomatic heart failure. Our study demonstrates that myocardial deformation analysis enables detection of early and progressive subclinical cardiac dysfunction, and GLS at 3 months was positively correlated to LVEF drop at 12 months.

Abstract P5-07-08: Evaluating the risk of cardiotoxicity associated with concurrent trastuzumab emtansine (TDM1) and radiation therapy in patients with early-stage HER2 positive breast cancer

Abstract BACKGROUND: HER2-positive breast cancers, which accounts for 20% of breast cancers, is associated with aggressive clinical behavior and inferior survival. The approval of HER2 targeted therapy has changed the landscape of this disease and has reduced disease recurrence by 50% and has improved survival by 33%. (1) However, cardiotoxicity is a well-recognized adverse event associated with HER2-targeted therapies. Adjuvant trastuzumab emtansine (TDM1) is the current standard of care for patients with residual breast cancer after neoadjuvant HER2-targeted therapy. TDM1 is associated with a risk of cardiotoxicity defined as a decline in left ventricular ejection fraction (LVEF). In a pooled analysis of data from seven metastatic breast cancer trials with TDM1, the incidence of cardiac events such as congestive heart failure (CHF), cardiac ischemia, cardiac arrhythmia or grade 1/2 LVEF drop was 3.37%. Adjuvant breast radiation (RT) is routinely offered for patients at high risk for recurrence. Breast RT is also associated with long-term increased risk of cardiac disease more than 10 years after RT. The HERA trial which studied use of adjuvant trastuzumab showed that rates of cardiotoxicity were higher in patients receiving concurrent RT with trastuzumab (left sided &amp;gt; right sided breast cancer) compared to those who did not receive adjuvant RT, although not statistically significant. In the multivariate analysis, no treatment or baseline cardiovascular risk factors were strongly correlated with LVEF, but radiation therapy showed a borderline correlation (adjusted HR, 1.258; 95% CI, 1.00-1.58; P = .049). The risk of cardiotoxicity with concurrent TDM1 and RT has not been well studied. With increasing use of TDM1 in the adjuvant setting, it is important to understand the cardiotoxic effects of combination therapy in early-stage breast cancer. METHODS: We undertook a review of our clinical database to identify patients who received adjuvant TDM1 with concurrent RT for Stage I-III breast cancer from 1/2020 to 01/2022. Clinical parameters including age, date of diagnosis, history of cardiac disorders, echocardiogram findings, radiation dose, final pathologic stage and molecular subtypes of cancer were extracted. All patients had ejection fraction to monitor cardiac fraction. Global longitudinal strain (GLS), which is a more sensitive and reproducible indicator of cardiac dysfunction than LVEF, was also collected, if available. RESULTS: Of 32 patients identified in our retrospective analysis, two patients (6%) developed a drop in ejection fraction post radiation. Median age of patients was 57y. Majority of the patients were Caucasian (44%) followed by Hispanic (28%). 19 (60%) patients had right sided breast cancers and 13(40%) patients had left sided cancers. The mean pre-radiation ejection fraction was 60% and post radiation was 61%. Using paired t-testing, there was no statically significant difference in ejection fraction after radiation (p=0.343). Comparative GLS measurements were available for 16 patients and there was no statical difference with concurrent radiation (p=0.18). All patients tolerated radiation with mostly grade 2 skin dermatitis except four patients who had grade 3 skin dermatitis. One patient had to discontinue radiation early given grade 3 skin dermatitis. CONCLUSION: This institutional review of 32 patients suggests that adjuvant TDM1 with concurrent RT did not result in a significant change in ejection fraction or GLS. Most patients tolerated radiation without significant skin toxicities. One of the limitations of the study is the small sample size. A larger study should look at more broader conclusions; however this data has strong clinical implications. Cardiac Parameters pre and post RT Citation Format: Faheem Farooq, Dillon Cason, Nisha Ohri, Shicha Kumar, Allison Grann, Anna Litvak, Shridar Ganesan, Bruce G. Haffty, Deborah Toppmeyer, Coral Omene, Mridula A. George. Evaluating the risk of cardiotoxicity associated with concurrent trastuzumab emtansine (TDM1) and radiation therapy in patients with early-stage HER2 positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-07-08.

Baseline Troponin Level and Cardiac Toxicity in HER2-positive Early Breast Cancer Patients Receiving Trastuzumab.

There is controversy around the use of high-sensitive troponin T (hs-TnT) as an early biomarker of cardiac toxicity in patients with breast cancer on trastuzumab (T). Patients receiving adjuvant or neo-adjuvant T for early HER2-positive breast cancer were prospectively included. Transthoracic echocardiograms and matched hs-TnT before T and at 3, 6, and 9 months were performed on all patients. Congestive heart failure, cardiac death, a decline in left ventricular ejection fraction (LVEF) of more than 10% from baseline even if it is still within the normal range, or a drop in LVEF below 55% were all considered signs of cardiac toxicity. In total, 24 patients (median age: 57; range=39-79 years) were enrolled. Anthracyclines were administered to all patients but three as part of neo/adjuvant treatment before T. Cardiovascular toxicity was observed in 3 out of 24 (12.5%) patients: two non-symptomatic LVEF declines (8.3%) and one heart failure episode (4.2%). In the entire population, the mean baseline hs-TnT level was 10.1±8.8 pg/ml, and after 3, 6, and 12 months, no appreciable change was observed. Patients with cardiac toxicity had mean hs-TnT levels higher than those without (18.3±12.3 vs. 8.2±7.2 pg/ml; p=0.049). A definite trend was evident in the chi-square test (chi2=3.52; p=0.06). In anthracycline-exposed patients with early breast cancer, hs-TnT may be able to identify those at risk of developing cardiac toxicity during neo/adjuvant T treatment.

Abstract 10869: Late Pericardial Effusion After Resolution of Takotsubo Cardiomyopathy in Covid-19 Infection. A Rare but Life-threatening Complication

Background: Various cardiac complications such as cardiomyopathy and sudden cardiac death have been associated with Coronavirus disease 2019 (COVID-19) pandemic. We present a case of late pericardial effusion after resolution of takotsubo cardiomyopathy in COVID-19. Case Report: A 46-year-old male presented with acute hypoxic respiratory failure secondary to COVID-19 pneumonia. His left ventricular ejection fraction (LVEF) was 55% at admission. Over the next two days, his condition worsened requiring mechanical ventilation and inotropic support. A repeat echocardiogram revealed severe biventricular systolic dysfunction with basal hypercontractility and a drop in LVEF to 25%. Cardiac catheterization showed clean coronaries, elevated filling pressures, and reduced cardiac index (CI:1.44L/min/m 2 ); hence cardiogenic shock secondary to viral myocarditis/takotsubo cardiomyopathy was suspected and an impella was placed. His condition improved with high-dose steroids, diuretics, and heart failure medication. He was subsequently weaned off circulatory and inotropic support and LVEF improved to 60% in four days, hence a provisional diagnosis of takotsubo cardiomyopathy was made. However, three days post-Impella removal he became tachycardic and hypotensive and a repeat echocardiogram showed moderate pericardial effusion with purulent material and Right Ventricle (RV) free wall diastolic collapse(image). He underwent emergent pericardiocentesis draining 800 ml of purulent fluid with pericardial drain placement. Pericardial fluid cultures returned negative. Thereafter, his condition significantly improved and he was discharged on hospital day 15. Conclusion: Symptomatic pericardial effusion can occur late in the clinical course even after other cardio-pulmonary symptoms have improved. This case highlights the importance of clinician awareness of the various cardiac complications in COVID-19 and their timely diagnosis and management.

Abstract 12791: Examining the Association Between Socioeconomic Factors and Left Ventricular Ejection Fraction Declines in Breast Cancer and Lymphoma Survivors Receiving Doxorubicin: WF-98213

Introduction: Breast cancer and lymphoma survivors who have received doxorubicin are at risk of experiencing a decline in left ventricular ejection fraction (LVEF), yet whether socioeconomic factors further impact this decline is unknown. Methods: We performed a secondary analysis of data from a double-blinded clinical trial (NCT01988571) in breast cancer and lymphoma survivors that determined the impact of statin use on LVEF 6- and 24-months following initiation of doxorubicin. LVEF was measured via magnetic resonance imaging. Socioeconomic factors were collected via survey. Linear regression models assessed relationships between socioeconomic variables and change in LVEF from baseline to 24 months by individuals blinded to treatment group. Results: Of the 279 survivors included in this analysis, a majority were white (82.8%) (13.6% Black, 3.6% other races), college educated (56.3%), and employed (63.8%). Mean LVEF at baseline was 62.2% (SD=6.01) and mean LVEF declines at 6- and 24-months were 4.72% (SD=7.30) and 5.11% (SD=7.20), respectively. In the multivariable model, after controlling for age, race, body mass index, and smoking, patients who made &gt;$75k per year had a significantly smaller LVEF drop (3.36, 95% CI: -0.53, 7.25) at 6-months than patients making less than &lt;$35k per year (8.66, 95% CI: 4.87, 12.45), p =0.003. Employed patients making &gt;$75k per year had significantly smaller LVEF declines (mean=5.00, 95% CI: 0.14, 9.86) than employed patients making less than 35k per year (mean=9.43, 95% CI: 4.30, 14.56), p=0.033. Lastly, employed patients making &gt;75k had a marginally significantly lower EF drop than unemployed patients making &gt;75k per year (mean=7.83, 95%CI: 3.32, 12.34), p=0.092. These findings occurred independent of statin use. Conclusions: Findings from this study highlight a need to understand how one’s socioeconomic status (SES), or in terms of social determinants of health, economic stability, may serve as a protective factor regarding LVEF decline during treatment with doxorubicin for breast cancer and lymphoma. Future work should also consider examining the association between SES and care delivery and how that may potentially impact LVEF decline.

Response to heart failure treatment in patients with anthracyclines and trastuzumab induced left ventricular dysfunction

Abstract Background Chemotherapy treatments with anthracyclines and Trastuzumab are widely used in different hematologic or solid malignancies but myocardial injury and left ventricular dysfunction, usually called cardiotoxicity (CTX), is a frequent adverse effect. Some studies have demonstrated that early detection and treatment of CTX is essential for the recovery of left ventricular ejection fraction (LVEF), however its behavior after starting treatment is not well established. Purpose Evaluate the behavior of LVEF after starting treatment for heart failure in patients with diagnosis of CTX. Methods Patients with diagnosis of solid or hematologic malignancies scheduled to receive therapy including anthracyclines and/or trastuzumab were prospectively included. Echocardiogram was performed before starting treatment, and then 3 and 6 months after. CTX was defined, according to guidelines, as a drop of LVEF ≥10% to a value &amp;lt;53% and in these patients treatment of left ventricular dysfunction with B blockers and Enalapril/Losartan was promptly initiated and up-titrated to the maximal tolerated dose. Myocardial injury was defined as a drop of LVEF ≥10% and a value ≥53%, with a watchful waiting strategie, considering these patients as a control group. LVEF was re-evaluated 6 months after starting treatment or after diagnosis of myocardial injury. Primary endpoint was defined as a recovery of LVEF ≥10%. Results Of a total of 141 patients of the entire cohort (mean age 56±15 years, 85,8% women and 61,7% with diagnosis of breast cancer),17 patients (12%) met criteria of CTX and 21 (14,9%) of myocardial injury. There were no differences in relation to clinical characteristics or chemotherapy schemes between groups. In patients with CTX (intervention group), 88,2% reached the primary endpoint of recovery of LVEF ≥10% while only 23,8% did it in the control group (p&amp;lt;0,001). Patients with CTX had lowest LVEF at baseline, however no significant differences were observed at 12 months of follow up. Figure 1 represents the behavior of LVEF at baseline, 3, 6 and 12 months. A paired before-after analysis was performed between LVEF at baseline and at 12 months. Patients who received treatment showed no differences in LVEF (63,3±7,2% vs 61,5±9,6%, p=0,5). In contrast, patients who did not receive treatment showed a significant drop in LVEF (72,7±4,4% vs 66,2±5,4%; p&amp;lt;0,001) (figure 2). Conclusion Treatment of left ventricular dysfunction in patients with CTX is associated with a greater recovery of LVEF. Funding Acknowledgement Type of funding sources: None.

Cardiotoxicity is mitigated after a supervised exercise program in HER2-positive breast cancer undergoing adjuvant trastuzumab.

BackgroundTrastuzumab is used, alone or in conjunction with standard chemotherapy, to treat HER2-positive breast cancer (BC). Although it improves cancer outcomes, trastuzumab. can lead to cardiotoxicity. Physical exercise is a safe and effective supportive therapy in the management of side effects, but the cardioprotective effects of exercise are still unclear.ObjectivesThe primary aim of this study was to test whether trastuzumab-induced cardiotoxicity [left ventricular ejection fraction (LVEF) under 50%, or an absolute drop in LVEF of 10%] was reduced after a supervised exercise program of 3 months in patients with HER2-positive breast cancer. Secondary endpoints were to evaluate (i) cardiotoxicity rates using other criteria, (ii) cardiac parameters, (iii) cardiorespiratory fitness and (iv) whether a change in LVEF influences the cardiorespiratory fitness.Methods89 women were randomized to receive adjuvant trastuzumab in combination with a training program (training group: TG; n = 46) or trastuzumab alone (control group: CG; n = 43). The primary and secondary endpoints were evaluated at the end of the supervised exercise program of 3 months (T3).ResultsAfter exercise program, 90.5 % of TG patients and 81.8% of CG patients did not exhibit cardiotoxicity. Furthermore, whatever the used criterion, percentage of patients without cardiotoxicity were greater in TG (97.6 and 100% respectively) than in CG (90.9 and 93.9% respectively). LVEF and GLS values remained stable in both groups without any difference between the groups. In contrast, at T3, peak VO2 (+2.6 mL.min−1.kg−1; 95%CI, 1.8 to 3.4) and maximal power (+21.3 W; 95%CI, 17.3 to 25.3) increased significantly in TG, whereas they were unchanged in CG (peak VO2: +0.2 mL.min−1.kg−1; 95%CI, −0.5 to 0.9 and maximal power: +0.7 W, 95%CI, −3.6 to 5.1) compared to values measured at T0. No correlation between LVEF changes and peak VO2 or maximal power was observed.ConclusionA 12-week supervised exercise regimen was safe and improved the cardiopulmonary fitness in particular peak VO2, in HER2-positive BC patients treated with adjuvant trastuzumab therapy. The study is under powered to come to any conclusion regarding the effect on cardiotoxicity.Clinical trial registrationwww.ClinicalTrials.gov, identifier: NCT02433067.

Is there a window of opportunity to optimize trastuzumab cardiac monitoring?

BACKGROUNDIt remains unclear whether the current arbitrary screening recommendations of trastuzumab-related cardiotoxicity provides an adequate balance between preventing heart damage and curtailing a curative treatment.AIMTo determine the incidence rate and consequences of trastuzumab-induced cardiotoxicity as adjuvant treatment in a real-world scenario.METHODSWe present a retrospective analysis of cardiac function measured by echocardiogram at baseline and every 3 mo during trastuzumab treatment. Cardiotoxicity was defined as a drop in left ventricular ejection fraction (LVEF) ≥ 10% from baseline and/or any drop < 50%. RESULTSBetween January 2011 and December 2014, 407 patients were selected. Most (93.6%) were treated with an anthracycline followed by a taxane-based regimen and trastuzumab for 12 mo. Forty patients (9.8%) had cardiotoxicity. None of them were symptomatic, and 28 (72.5%) completely recovered LVEF. Cardiotoxicity happened early as shown by LVEF measured on echocardiogram 2 to 4 as compared to 5 to 7 (odds ratio = 2.47, 95% confidence interval: 1.09, 5.63, P = 0.024). There were 54 deaths (13.3%) during the 70-mo follow-up period; 1 (0.2%) was attributed to late cardiotoxicity (4 years after treatment). The absence of symptomatic cardiotoxicity during trastuzumab treatment and moreover the early occurrence on the treatment period may translate into a strategy to evaluate less frequently.CONCLUSIONWe observed a 10% rate of asymptomatic cardiotoxicity, which mirrors the results from the large adjuvant trials. Despite being transient, an LVEF drop led to frequent treatment delays and interruptions. It remains unclear whether LVEF decline is predictive of late cardiotoxicity, and treatment efficacy is compromised.

Prognostic value of absent left ventricular ejection fraction reserve with regadenoson SPECT MPI

BackgroundAn absent left ventricular ejection fraction (LVEF) reserve with vasodilator stress with PET cardiac imaging has been shown to provide significant independent and incremental value to the perfusion images for prediction of future cardiovascular adverse events. However, the prognostic value of LVEF reserve has not been well characterized with SPECT myocardial perfusion imaging (MPI). MethodsWe studied 858 consecutive patients with normal and abnormal perfusion pattern with regadenoson SPECT MPI. Change in LVEF was calculated as post-stress LVEF—rest LVEF. Absent LVEF reserve was defined as a drop in LVEF by 5% or more on the post-stress images. The primary outcome was a composite of cardiac death, non-fatal myocardial infarction and late coronary revascularization. ResultsAn absent LVEF reserve was more common in patients with abnormal vs normal MPI (31% vs 19%, P = .001). During a median follow-up of 32 months, the primary outcome was experienced by 31% of the study population. An absent LVEF reserve was not associated with an increased risk of the primary outcome in patients with normal (hazard ratio 1.1, 95% CI .4-2.7, P = .8) or abnormal (.75, .56-1.00, P = .05) MPI. There was no significant correlation between extent of ischemia and post-stress change in LVEF (Pearson r = − .072, P = .07). ConclusionsIn patients undergoing regadenoson SPECT MPI, absent LVEF reserve is not associated with worse cardiac outcomes. Thus, routine reporting of both post-stress and rest LVEF measurements in this setting may not be necessary.